Twenty-four-hour urinary protein excretion in uncomplicated singleton pregnancy.

BACKGROUND: Twenty-four-hour urinary total protein excretion is an essential parameter used for evaluation of renal function and early detection of gestational complications. However, data on reference ranges of 24-hour urinary total protein excretion in normal pregnancy are scarce. OBJECTIVE: This study aimed to determine reference ranges for 24-hour urinary total protein excretion in a population with uncomplicated singleton pregnancies using a standard method for urinary total protein. In addition, the values of 24-hour urinary total protein were stratified by maternal age and prepregnancy body mass index. STUDY DESIGN: This study was based on a prospective cohort study in Shenzhen, China. The pregnant women were enrolled at their first prenatal clinical visit. All the participants were instructed to collect 24-hour urine samples during the following successive gestational periods: 6+0 to 13+6, 14+0 to 27+6, and 28+0 to 41+6 weeks. Total urinary protein excretion was analyzed by a colorimetric method. Ultimately, the study encompassed a total of 4844 pregnant women with uncomplicated pregnancies. The nonparametric percentile method was used to determine reference ranges for 24-hour urinary total protein excretion during different trimesters in women with uncomplicated pregnancies (excluding those with previous kidney disorders, gestational or chronic hypertension, preeclampsia, and pregestational diabetes mellitus, among others). RESULTS: The 24-hour urinary total protein levels expressed as medians and percentiles (5th, 95th) for each trimester were as follows: 72.0 (28.4, 165.0), 88.0 (34.0, 185.0), and 108.0 (37.5, 258.0) mg in the first, second, and third trimesters, respectively. A significant increase in 24-hour urinary total protein excretion was observed throughout pregnancy (all P values <.001). Moreover, 24-hour urinary total protein levels were higher in the older (≥35 years) than in the younger (<35 years) group from mid-gestation. Specifically, the median (interquartile range) 24-hour urinary total protein levels by age were 72.2 (50.6-100.0) vs 70.5 (50.5-100.0) mg, 85.8 (62.0-117.0) vs 96.0 (68.0-127.8) mg, and 106.6 (76.0-146.2) vs 114.7 (81.5-153.6) mg in the first, second, and third trimesters, respectively. In addition, 24-hour proteinuria was significantly increased in higher-weight (overweight or obese) subgroups compared with lower-weight (underweight or normal-weight) subgroups (all P values <.05). CONCLUSION: Our study provides reference values for 24-hour urinary total protein excretion with apparently uncomplicated pregnancies. Understanding these changes in low-risk pregnancies is essential for optimizing maternal management.

The correlation between the thyroid function and urinary iodine/creatinine ratio of pregnant women attending a tertiary hospital in Beijing, China, during different trimesters.

OBJECTIVE: This study investigated the correlation between thyroid function and urinary iodine/creatinine ratio (UI/Cr) in pregnant women during different trimesters and explored potential influencing factors. METHODS: In this cross-sectional study, serum levels of thyroid-stimulating hormone (TSH), free triiodothyronine (FT3), free thyroxine (FT4), and UI/Cr were measured in 450 pregnant women. Correlations were analyzed using Pearson's correlation coefficient and multiple linear regression. Subgroup analyses were performed based on age, body mass index (BMI), parity, gestational age, education, occupation, and family history of thyroid disorders. RESULTS: UI/Cr was positively correlated with FT4 levels in the first and second trimesters, particularly in women with older age, higher BMI, multiparity, higher education, and employment. No significant correlations were found between UI/Cr and TSH or FT3 levels. CONCLUSION: UI/Cr is positively correlated with FT4 levels in early pregnancy, especially in women with certain risk factors. Regular monitoring of iodine status and thyroid function is recommended for pregnant women to ensure optimal maternal and fetal health.

Iodine monitoring models contribute to avoid adverse birth outcomes related more than adequate iodine intake.

BACKGROUND: Iodine plays an important role in pregnancy. How to maintain adequate iodine intake amongst pregnant women in each trimester of pregnancy to prevent adverse birth outcomes in central China is a challenge for clinical practice. METHODS: 870 pregnant women and their infants were enrolled in the study. Urinary iodine concentration (UIC) was measured using an inductively coupled plasma mass spectrometry (ICP-MS). Maternal and newborn information were obtained during follow-up. Multinomial logistic regression models were established. RESULTS: Median UIC of pregnant women was 172 ± 135 µg/L which is currently considered to be sufficient. Multivitamin supplements containing iodine, iodized salt intake and frequent milk intake were significantly associated with higher UIC. Multivariate logistic regression analysis showed that multivitamin supplements containing iodine and milk consumption were risk factors for more than adequate iodine (UIC ≥ 250 µg/L). Iodine-rich diet was significantly related to heavier birthweight, larger head circumference and longer femur length of the newborns while more than adequate iodine intake (UIC ≥ 250 µg/L) was a risk factor for macrosomia. Logistic regression models based on potential risk factors involving iodine containing supplements and iodine-rich diet were established to predict and screen pregnant women with high risk of more than adequate iodine intake among local pregnant women in different trimesters and guide them to supplement iodine reasonably to prevent the risk. CONCLUSIONS: Multivitamin supplements containing iodine and milk consumption were risk factors for maternal UIC ≥ 250 µg/L which was a risk factor for macrosomia. Iodine monitoring models were established to provide guidance for pregnant women to reduce the risk of more than adequate iodine intake, thereby contributing to reduce the risk of having a macrosomia.

Relationship of household cooking salt and eating out on iodine status of pregnant women in environmental iodine-deficient coastal areas of China.

As city residents eat out more frequently, it is unknown that if iodised salt is still required in home cooking. We analysed the relationship of household salt and eating out on urinary iodine concentration (UIC) in pregnant women. A household condiment weighing method was implemented to collect salt data for a week. A household salt sample was collected. A urine sample was taken at the end of the week. Totally, 4640 participants were investigated. The median UIC was 139·1 µg/l in pregnant women and 148·7, 140·0 and 122·9 µg/l in the first, second and third trimesters. Median UIC in the third trimester was lower than in the other trimesters (P < 0·001). The usage rates of iodised (an iodine content ≥ 5·0 mg/kg) and qualified-iodised (an iodine content ≥ 21·0 mg/kg) salt were 73·9 and 59·3 %. The median UIC in the qualified-iodised salt group was higher than in the non-iodised group (P = 0·037). The median UIC in the non-iodised group who did not eat out was lower than in qualified-salt groups who both did and did not eat out (P = 0·007, <0·001). The proportion of qualified-iodised salt used in home cooking is low, but foods eaten out have universal salt iodisation according to the national compulsory policy. Household iodised salt did not play a decisive role in the iodine status of pregnant women. Pregnant women in their third trimester who are not eating out and using non-iodised salt at home require extra iodine.

A cross-sectional research of iodine status of pregnant women in Chongqing, south-west China.

OBJECTIVE: To investigate whether implementation of a universal salt iodization (USI) programme has sufficient effects on pregnant women in Chongqing, the present study evaluated the iodine nutritional status of pregnant women living in Chongqing by spot urinary iodine concentration (UIC), to provide scientific suggestions to better meet the specific iodine needs of this vulnerable group. DESIGN: Cross-sectional design. SETTING: A random spot urine sample and household table salt sample were provided by each participant. PARTICIPANTS: A total of 2607 pregnant women from twenty-six of thirty-nine districts/counties in Chongqing participated. RESULTS: The overall median UIC of pregnant women was 171·80 µg/l (interquartile range (IQR) = 113·85-247·00 µg/l) and 40·97 % (n 1057) of participants were iodine insufficient. The median iodine in table salt samples was 25·40 mg/kg (IQR = 23·10-28·30 mg/kg); 93·26 % (n 2406) of samples examined were found to be adequately iodized. Iodine nutritional status was not significantly different according to table salt iodization category. Trimester was identified to be statistically associated with UIC (P < 0·01). Seven districts/counties had median UIC below 150 µg/l and one district had median UIC of 277·40 µg/l. CONCLUSIONS: The USI programme in Chongqing prevents iodine deficiency generally, but does not maintain iodine status within adequate and recommended ranges throughout pregnancy. Usage of non-iodized or unqualified iodized salt and the slight change of dietary habits of iodized salt in Chongqing may present a substantial challenge to fight iodine-deficiency disorders; more efforts are needed to ensure adequate iodine intake during pregnancy besides the USI programme.

Trimester-Specific Thyroid Function in Pregnant Women with Different Iodine Statuses.

OBJECTIVES: To explore trimester-specific thyroid function changes under different iodine statuses throughout pregnancy. METHODS: A cross-sectional study was conducted to assess the pregnancy iodine status, and 2,378 healthy pregnant women covering all 3 trimesters were recruited. Urinary iodine concentration (UIC) was measured by collecting spot urine samples. Blood samples were collected to evaluate thyroid function. Thyroid B-ultrasonography was conducted to measure the thyroid volume (Tvol). RESULTS: The median UIC was 168 µg/L (111-263 µg/L). The UIC, free triiodothyronine (FT3), and free thyroxine (FT4) were significantly decreased as the pregnancy progressed (p < 0.001, p for trend <0.001), while Tvol increased (p < 0.001, p for trend <0.001). Thyrotropin (TSH) was significantly different between the 3 trimesters and showed an upward trend (p < 0.001), but the p for trend was not significant (p for trend = 0.88). After stratification by UIC, there were no significant differences in serum TSH, FT4, or FT3 level between UIC groups. Tvol was significantly higher in the UIC ≥500 µg/L group in the first trimester (ß: 2.41, 95% CI: 1.09-3.72, p <0.001), as well as in the 250 ≤ UIC < 500 µg/L group (ß: 1.65, 95% CI: 0.61-2.70, p < 0.001) and UIC ≥500 µg/L group (ß: 3.35, 95% CI: 1.96-4.74, p < 0.001) in the third trimester. CONCLUSIONS: No difference was observed in TSH, FT3, or FT4 among the different iodine status groups throughout pregnancy. Tvol increased as the pregnancy progressed, and it was especially higher in the UIC ≥500 µg/L group in the first and third trimesters.

Iodine deficiency among pregnant women living in Northern Ireland.

OBJECTIVE: Mild iodine deficiency has re-emerged among school girls in the UK. We wished to study a contemporaneous pregnant population because a relationship between maternal iodine deficiency and offspring cognitive scores has recently been reported. The WHO has set a median population urinary iodine concentration (UIC) of ≥100 and ≥150 µg/L to define adequacy outside of and during pregnancy, respectively. Iodine creatinine ratio (ICR) is also used to correct for dilution effects (sufficiency ≥150 µg/g creatinine in pregnancy). DESIGN AND METHODS: A total of 241 women were followed across trimesters (T) into the postpartum period (PPP) along with 80 offspring with spot urine sampling and food frequency questionnaires. RESULTS: Median UIC was 73 µg/L in the 1st T (ICR 102 µg/g creatinine) despite 55% taking iodine-containing supplements. Median UICs were 94, 117 and 90 µg/L in the 2nd T, 3rd T and PPP, respectively. Corresponding ICRs were 120, 126 and 60 µg/g creatinine. ICR was associated with volume of milk consumed throughout pregnancy. Median UIC among the offspring was 148 µg/L, with no difference between the breast- and formula-fed babies. CONCLUSIONS: Pregnant women living in Northern Ireland may be at risk of iodine deficiency across pregnancy and into the PPP while the offspring are iodine sufficient. This is the first study of its kind in the UK with data for pregnant women and their offspring. The UK does not provide an iodine fortification programme nor offer routine iodine dietary advice in pregnancy and this requires consideration by public health agencies.

Early pregnancy bisphenol and phthalate metabolite levels, maternal hemodynamics and gestational hypertensive disorders.

STUDY QUESTION: Are early-pregnancy urinary bisphenol and phthalate metabolite concentrations associated with placental function markers, blood pressure (BP) trajectories during pregnancy and risk of gestational hypertensive disorders? SUMMARY ANSWER: Early-pregnancy bisphenols and phthalate metabolites were not consistently associated with maternal BP changes or gestational hypertensive disorders, but subclinical, statistically significant associations with placental angiogenic markers and placental hemodynamics were identified. WHAT IS KNOWN ALREADY: In vitro studies suggest that bisphenols and phthalate metabolites may disrupt early placental development and affect the risk of gestational hypertensive disorders. Previous studies investigating effects of bisphenols and phthalate metabolites on gestational hypertensive disorders reported inconsistent results and did not examine placental function or BP throughout pregnancy. STUDY DESIGN, SIZE, DURATION: In a population-based prospective cohort study, bisphenol and phthalate metabolite concentrations were measured in a spot urine sample in early pregnancy among 1396 women whose children participated in postnatal follow-up measurements. PARTICIPANTS/MATERIALS, SETTING, METHODS: After exclusion of women without any BP measurement or with pre-existing hypertension, 1233 women were included in the analysis. Urinary bisphenol and phthalate metabolite concentrations were measured in early-pregnancy [median gestational age 13.1 weeks, inter-quartile range 12.1-14.5]. Molar sums of total bisphenols and of low molecular weight phthalate, high molecular weight (HMW) phthalate, di-2-ethylhexylphthalate, and di-n-octylphthalate metabolites were calculated. Placental angiogenic markers (placental growth factor (PlGF), soluble fms-like tyrosine kinase (sFlt)-1), placental hemodynamic function measures (umbilical artery pulsatility index (PI), uterine artery resistance index (RI), notching and placental weight), and maternal BP were measured in different trimesters. Information on gestational hypertensive disorders was obtained from medical records. MAIN RESULTS AND THE ROLE OF CHANCE: Each log unit increase in HMW phthalate metabolites was associated with a 141.72 (95% CI: 29.13, 373.21) higher early pregnancy sFlt-1/PlGF ratio (range in total sample 9-900). This association was driven by mono-[(2-carboxymethyl)hexyl]phthalate. In the repeated measurements regression models, each log unit increase in bisphenol A was associated with a 0.15 SD (95% CI: 0.03, 0.26) higher intercept and -0.01 SD (95% CI: -0.01, -0.00) decreasing slope of the umbilical artery PI Z-score and a -1.28 SD (95% CI: -2.24, -0.33) lower intercept and 0.06 SD (95% CI: 0.02, 0.11) increasing slope of the uterine artery RI Z-score. These associations remained significant after Bonferroni correction. Early-pregnancy bisphenols or phthalate metabolites showed no consistent associations with any other outcome. LIMITATIONS, REASONS FOR CAUTION: Information on a large number of potential confounders was available but was partly self-reported. Bisphenols and phthalate metabolites, which typically have a half-life of 24-48 h, were measured via single spot urine samples in early-pregnancy. In addition, at the current sample size, the study was powered to detect an odds ratio of 1.57 for gestational hypertension and 1.78 for pre-eclampsia, but was underpowered to perform multivariable analyses for these outcomes. Further studies combining data from different cohorts may be necessary to increase power. These limitations are possible sources of non-differential misclassification leading to bias toward the null. WIDER IMPLICATIONS OF THE FINDINGS: Bisphenols and phthalate metabolites were not associated with longitudinal changes in BP in pregnancy in our low-risk population. The observed subclinical associations of phthalates with the sFlt-1/PlGF ratio and of bisphenol A with placental hemodynamics may contribute to adverse pregnancy outcomes. Our results are therefore more supportive of an association of early pregnancy bisphenols and phthalate metabolites with risk for pre-eclampsia than with gestational hypertension. STUDY FUNDING/COMPETING INTEREST(S): This analysis was supported by Grant (ES022972) from the National Institutes of Health, USA. The content is solely the responsibility of the authors and does not represent the official views of the National Institutes of Health. The authors report no conflicts of interest.

Reference Intervals for Urine Sediment Analysis of Healthy Pregnant Women.

BACKGROUND: Urine sediment parameters of pregnant women are different from those of non-pregnant women, and it is necessary to establish reference intervals for pregnant women. The aim of this study was to establish reference intervals of white blood cell (WBC), red blood cell (RBC), bacteria (BACT), squamous epithelial cell (EC), small round epithelial cell (SRC), and mucous strands (MUS) for urine sediment test of pregnant women using a UF-1000i analyzer as the detection device. The differences between pregnant women and non-pregnant women in terms of the aforementioned parameters as well as the differences of such parameters in different trimesters of pregnancy were clarified. METHODS: The experimental subjects were divided into two groups: the experiment group (612 healthy pregnant women) and the control group (582 healthy non-pregnant women). Subjects of both groups are women between the age of 22 and 46. The urine specimens were analyzed using the Sysmex UF-1000i analyzer, followed by manual correction. A statistical analysis was performed by SPSS 22.0. Results were considered significant at p < 0.01. RESULTS: The pregnancy reference intervals of WBC, RBC, BACT, EC, SRC, and MUS were 0 ~ 30/µL, 0 ~ 23/µL, 0 ~ 698/µL, 0 ~ 28/µL, 0 ~ 8/µL, and 0 ~ 3/µL, respectively. In the experiment group, the concentrations of WBC, BACT, EC, and SRC were significantly higher than those of the control group (p < 0.01), while the concentrations of RBC and MUS were significantly lower than those of the control group (p < 0.01). The inter-trimester differences in terms of the concentrations of WBC, BACT, EC, and SRC were statistically indistinguishable (p > 0.05). However, the concentration of RBC was significantly lower with the increase of trimester of pregnancy (the comparison between the first trimester with the second trimester: p = 0.000 < 0.01; the comparison between the second trimester and the third trimester: p = 0.004 < 0.01). The WBC, BACT, EC, and SRC had moderate intercorrelations (0.569 ~ 0.681, p < 0.01). CONCLUSIONS: There were significant differences in the aforementioned parameters between the two groups. The intervals of WBC, RBC, BACT, EC, SRC, and MUS for urine sediment analysis of healthy pregnant women using a UF-1000i should be established.

Effect of urine creatinine level during pregnancy on dipstick test.

AIM: Dipstick results for proteinuria are affected by urine concentration, and thus urine creatinine concentration ([Cr]). This study was performed to determine whether spot urine [Cr] changes significantly during pregnancy, leading to a significantly different false-negative rate (FNR) on dipstick test between trimester. METHODS: The [Cr] and protein concentrations ([P]) were analyzed in 631 spot urine samples with negative/equivocal dipstick from 425 pregnant women. False-negative dipstick was defined as [P] : [Cr] ratio (P/Cr) > 0.27 mg/mg. RESULTS: Median [Cr] was 117 mg/dL (range, 6.5-326 mg/dL), 72 mg/dL (range, 4.3-477 mg/dL), and 73 mg/dL (range, 8.4-396 mg/dL) in the first (n = 96), second (n = 344), and third (n = 191) trimester urine samples, respectively (P = 0.000, Kruskal-Wallis). Both [P] and P/Cr increased significantly with advancing gestation. FNR 9.4% (18/191) in the third trimester was significantly higher than that of 0.0% (0/96) in the second trimester and that of 0.5% (2/344) in the third trimester. In the 20 urine samples with false-negative dipstick, median [Cr] was 47.0 mg/dL (range, 11.0-358 mg/dL) and the proportion of samples with dilute urine, that is, [Cr] <47 mg/dL, was significantly higher than in the remaining 611 urine samples (50%, 10/20 vs 28%, 174/611, respectively, P = 0.046). CONCLUSIONS: Urine samples in the second and third trimesters were more likely to be diluted compared with the first trimester. This was associated with high FNR in third trimester urine samples.

Dietary determinants of urinary molybdenum levels in Mexican women: a pilot study.

OBJECTIVE: This study determined the main dietary sources of urinary molybdenum (Mo) concentrations in a sample of 124 pregnant women in Mexico. MATERIALS AND METHODS: Dietary data was collected during pregnancy, through a semi-qualitative food frequency questionnaire, with information of 84 foods. Urine Mo levels were determined by atomic absorption spectrometry, for at least two trimesters of pregnancy. The associations with Mo levels were estimated by generalized mixed effect regression models. RESULTS: Between 5.8 to 12.7% of the samples were above the 95th percentile of urinary Mo distribution reported by National Health and Nutrition Examination Survey (NHANES) 2009-2010 for women (151 µg/L and 148 µg/g creatinine). After bootstrap resampling was conducted, women with high-consumption of hot peppers (ß=1.34µg/g; 95% CI: 1.00-1.80; p= 0.05) had marginally higher urinary Mo concentration levels, creatinine adjusted, compared to women with low-consumption. CONCLUSION.: Hot chili pepper consumption may contribute to body burden Mo levels in this population.

Maternal creatine in pregnancy: a retrospective cohort study.

OBJECTIVE: To estimate creatine concentrations in maternal plasma and urine, and establish relationships with maternal characteristics, diet and fetal growth. DESIGN: Retrospective cohort study. SETTING: Lyell McEwin Hospital, Adelaide, Australia. POPULATION: A biobank of plasma and urine samples collected at 13, 18, 30 and 36 weeks' gestation from 287 pregnant women from a prospective cohort of asthmatic and non-asthmatic women. METHODS: Creatine was measured by enzymatic analysis. Change in creatine over pregnancy was assessed using the Friedman test. Linear mixed models regression was used to determine associations between maternal factors and diet with creatine across pregnancy and between creatine with indices of fetal growth at birth. MAIN OUTCOME MEASURES: Maternal creatine concentrations, associations between maternal factors and creatine and between creatine and fetal growth parameters. RESULTS: Maternal smoking, body mass index, asthma and socio-economic status were positively and parity negatively associated with maternal plasma and/or urine creatine. Maternal urine creatine concentration was positively associated with birthweight centile and birth length. After adjustment, each µmol/l increase in maternal urinary creatine was associated with a 1.23 (95% CI 0.44-2.02) unit increase in birthweight centile and a 0.11-cm (95% CI 0.03-0.2) increase in birth length. CONCLUSIONS: Maternal factors and fetal growth measures are associated with maternal plasma and urine creatine concentrations. TWEETABLE ABSTRACT: Maternal creatine is altered by pregnancy; fetal growth measures are associated with maternal creatine concentrations.

Reduction of tobacco smoke exposure for pregnant passive smokers using feedback of urinary cotinine test results.

AIMS: Our objective was to evaluate the level of pregnant women's exposure to tobacco smoke by urinary cotinine testing at prenatal examinations, and to examine the effects of disclosing the results of urinary cotinine tests to pregnant women and their families on their smoking activities. METHODS: A prospective cohort study was conducted, enrolling 420 pregnant women who attended prenatal examinations at five private clinics in Japan. Urinary cotinine testing and a questionnaire survey regarding smoking status were conducted in early, middle, and late pregnancy. Urinary cotinine values were measured semiquantitatively using NicCheck I test strips. The results of each urinary cotinine test were handed to the pregnant woman and shared with her family. RESULTS: The percentages of urinary cotinine-positive subjects in middle and late pregnancy were significantly decreased compared with early pregnancy (P<0.001 each). Among the active smokers, there were no significant differences in the urinary cotinine-positive rates and the numbers of cigarettes among the three stages. In contrast, the urinary cotinine-positive rates in the passive smokers in late pregnancy were significantly lower than in early pregnancy (P=0.045) and those in non-smokers in middle and late pregnancy were also lower than in early pregnancy (P=0.001, P<0.001). The numbers of cigarettes smoked by persons close to the passive smokers in middle and late pregnancy were significantly lower than in early pregnancy (P<0.001). CONCLUSIONS: The feedback of the urinary cotinine test results at prenatal examinations decreased the level of exposure of pregnant passive smokers and non-smokers to tobacco smoke.

The microRNA spectrum in 12 body fluids.

BACKGROUND: MicroRNAs (miRNAs) are small, noncoding RNAs that play an important role in regulating various biological processes through their interaction with cellular messenger RNAs. Extracellular miRNAs in serum, plasma, saliva, and urine have recently been shown to be associated with various pathological conditions including cancer. METHODS: With the goal of assessing the distribution of miRNAs and demonstrating the potential use of miRNAs as biomarkers, we examined the presence of miRNAs in 12 human body fluids and urine samples from women in different stages of pregnancy or patients with different urothelial cancers. Using quantitative PCR, we conducted a global survey of the miRNA distribution in these fluids. RESULTS: miRNAs were present in all fluids tested and showed distinct compositions in different fluid types. Several of the highly abundant miRNAs in these fluids were common among multiple fluid types, and some of the miRNAs were enriched in specific fluids. We also observed distinct miRNA patterns in the urine samples obtained from individuals with different physiopathological conditions. CONCLUSIONS: MicroRNAs are ubiquitous in all the body fluid types tested. Fluid type-specific miRNAs may have functional roles associated with the surrounding tissues. In addition, the changes in miRNA spectra observed in the urine samples from patients with different urothelial conditions demonstrates the potential for using concentrations of specific miRNAs in body fluids as biomarkers for detecting and monitoring various physiopathological conditions.

Maternal gestational androgen levels in female marmosets (Callithrix geoffroyi) vary across trimesters but do not vary with the sex ratio of litters.

Maternal hormones can dramatically modify offspring phenotypes via organizational actions on morphological and behavioral development. In placental mammals, there is the possibility that some portion of hormones in maternal circulation may be derived from fetal origin. We tested the possibility that maternal androgens in pregnant female marmosets reflected, in part, contributions from male fetuses by comparing levels of urinary androgens across pregnancy in females carrying varying numbers of male offspring. We monitored urinary androgen excretion in 18 pregnancies from five female white-faced marmosets (Callithrix geoffroyi). Androgen levels rose significantly in the first trimester of pregnancy, reached a peak in the middle of the second trimester, and then declined gradually until parturition. At no point in pregnancy were levels of urinary androgens higher in females carrying litters that had 50% or more males than in females carrying litters that were less than 50% male. Levels of maternal androgens were not associated with litter size, the number of males in the litter, or with the proportion of the litter that was male. The high levels of androgen in pregnant females are therefore likely of strictly maternal origin, and any modification of fetal growth and development can be considered a 'maternal effect'.

High dietary calcium intake decreases bone mobilization during pregnancy in humans.

UNLABELLED: Calcium metabolism of the mother is modified during pregnancy because of the mineralization of the fetus skeleton. OBJECTIVE: To evaluate the association of calcium intake and bone demineralization during pregnancy. MATERIAL AND METHODS: At each trimester of pregnancy a validated food frequency intake questionnaire was administered to assess individual daily calcium intake in a cohort of 206 pregnant women, residents of Mexico City. Samples of urine were collected to measure levels of the cross-linked N-telopeptide of type I collagen (NTx), which is a biomarker of bone resorption. The association between calcium ingestion and bone resorption was analyzed using random effects models; non-linear associations were explored using generalized additive models. RESULTS: Progressive increases in NTx levels were observed during pregnancy; with mean and standard deviation (SD) values during the first, second and third trimester of 76.50 (SD=38), 101.02 (SD=48.86) and 144.83 (SD=61.33) nmol BCE/mmol creatinine, respectively. Higher dietary calcium intake was associated with lower bone resorption (beta=-0.015; p<0.05). The association between age and NTx showed a non-linear trend with an inflexion point around 33 years: increase in maternal age below that point was associated with a decrease in bone resorption, while in older women the increase in age was associated with an increased resorption. CONCLUSIONS: Our results suggest that calcium ingestion, specifically from dairy products, reduces bone resorption during pregnancy. For each 300 mg (a glass of milk) of calcium intake there is an estimated reduction in NTx level of 4.8 nmol BCE/mmol of creatinine (p<0.05).

Maternal urinary benzophenones and infant birth size: Identifying critical windows of exposure.

Benzophenones (BPs) are widely used as ultraviolet absorbers and fragrance retention agents. Evidences from animal studies have suggested that exposure to BPs may affect fetal growth, but human data is limited and no study is concerning critical windows of BPs exposure throughout pregnancy in relation to fetal growth. We aimed to investigate the associations of prenatal exposure to BPs with birth size and examine the critical exposure windows of fetus development. We measured BPs (including 2,4-dihydroxybenzophenone (BP-1), 2-hydroxy-4-methoxybenzophenone (BP-3) and 4-hydroxybenzophenone (4-OH-BP)) in maternal urine samples collected in the first, second, and third trimester from 847 mothers recruited in Wuhan, China. The general estimation equations were used to analyze the relationships between maternal exposure to BPs levels and birth size. In all newborns, we found each log unit increase in maternal urinary concentrations of BP-1 and 4-OH-BP in the 1st trimester were associated with decreases in birth length by 0.06 cm (95% confidence interval (CI): -0.11, -0.01) and 0.08 cm (95% CI: -0.15, -0.01), respectively, but only the association with BP-1 in the boys remained significant in the stratified analysis by infant sex. In girls, urinary concentrations of BP-1 and BP-3 in the 3rd trimester were associated with decreased birth weight (adjusted ß = -27.99 g, 95% CI: -50.66, -5.31 and -19.75 g, 95% CI: -37.31, -2.19, respectively) and length (adjusted ß = -0.08 cm, 95% CI: -0.17, 0.00 and -0.08 cm, 95% CI: -0.15, -0.02) (p for interaction = 0.04). Our findings indicate that maternal urinary levels of BPs in the early and late periods during pregnancy may have impacts on delayed fetal growth, and the effects were more pronounced in girls.

Association of Maternal Iodine Status With Child IQ: A Meta-Analysis of Individual Participant Data.

CONTEXT: Although the consequences of severe iodine deficiency are beyond doubt, the effects of mild to moderate iodine deficiency in pregnancy on child neurodevelopment are less well established. OBJECTIVE: To study the association between maternal iodine status during pregnancy and child IQ and identify vulnerable time windows of exposure to suboptimal iodine availability. DESIGN: Meta-analysis of individual participant data from three prospective population-based birth cohorts: Generation R (Netherlands), INMA (Spain), and ALSPAC (United Kingdom); pregnant women were enrolled between 2002 and 2006, 2003 and 2008, and 1990 and 1992, respectively. SETTING: General community. PARTICIPANTS: 6180 mother-child pairs with measures of urinary iodine and creatinine concentrations in pregnancy and child IQ. Exclusion criteria were multiple pregnancies, fertility treatment, medication affecting the thyroid, and preexisting thyroid disease. MAIN OUTCOME MEASURE: Child nonverbal and verbal IQ assessed at 1.5 to 8 years of age. RESULTS: There was a positive curvilinear association of urinary iodine/creatinine ratio (UI/Creat) with mean verbal IQ only. UI/Creat <150 µg/g was not associated with lower nonverbal IQ (-0.6 point; 95% CI: -1.7 to 0.4 points; P = 0.246) or lower verbal IQ (-0.6 point; 95% CI: -1.3 to 0.1 points; P = 0.082). Stratified analyses showed that the association of UI/Creat with verbal IQ was only present up to 14 weeks of gestation. CONCLUSIONS: Fetal brain development is vulnerable to mild to moderate iodine deficiency, particularly in the first trimester. Our results show that potential randomized controlled trials investigating the effect of iodine supplementation in women with mild to moderate iodine deficiency on child neurodevelopment should begin supplementation not later than the first trimester.

Comparison of urinary and plasma cotinine levels during the three trimesters of pregnancy.

Assays of metabolised cotinine are considered to be an accurate measure of exposure to cigarette smoke among pregnant women. We investigated the association and differences between the cotinine levels in maternal urine and blood, and the umbilical cord blood of three tobacco exposure groups at different stages of pregnancy. A prospective study was conducted among 398 pregnant women undergoing prenatal care in different trimesters at two medical centres and one regional hospital in central Taiwan. All 398 subjects (including 25 smokers, 191 passive smokers and 182 non-smokers) remained in the study up to the time of delivery; 384 of them delivered singleton live births. Cotinine levels were assayed in the maternal plasma and urine of the mothers at each trimester and in the cord blood of the newborns. All specimens were measured using a sensitive high-performance liquid chromatography. Cotinine concentrations in plasma and urine showed a significant dose-dependent difference among the three groups (non-smoker, passive and active smoker) and a trend that increased with gestation among the pregnant women. Significant correlations between cotinine concentrations in plasma and urine among the pregnant women in each trimester were found. In addition, the level of cotinine in umbilical cord blood was significantly correlated with that in maternal blood at term (r = 0.89, P < 0.001). A pattern of elevated cotinine concentrations in the plasma and urine of pregnant women from the beginning to the end of pregnancy was found, and this correlated significantly with the cotinine levels in the umbilical cord blood.

[The results of the "tiromobil" epidemiological trial of pregnant women in the Russian Federation].

AIM: To study structural and functional changes in the thyroid gland (TG) in pregnant women living in iodine-deficiency regions; to evaluate efficacy of prophylactic measures. MATERIAL AND METHODS: Random sample method was used for examination of 1090 pregnant women living in the regions with different iodine provision. All the participants were examined clinically, measurements were made of thyroid size, TTH, free T4, iodinuria. RESULTS: Iodine salt in household was used only by 17% women. Prophylaxis of iodine deficiency was conducted in 51% pregnant women. Thyroid alterations were detected in 27% examinees, diffuse goiter was diagnosed on the average in 17% pregnant women (in some regions 36%), nodular goiter--in 3.1%, focal goiter alterations of the thyroid--in 4.4%, symptoms of autoimmune thyroid disease--in 2.7%. ldoinuria varied with regions from 72.5 to 150 mcg/l. TTH and T4 levels were mainly normal. Isolated fall of T4 in trimester II and III was registered in 70% pregnant women, low TTH--in 4.4%. CONCLUSION: Most of the pregnant women in the regions studied were at risk of diseases associated with iodine deficiency. Prevention of iodine deficiency is not adequate.